Sandoz



s are always more or Patented June 16, 1931 9 TED. STATES PATENT OFFICE FRITZ F BASEIF, SWITZERLAND, ASSIGNOR'T'O CHEMICAL WORKS FORMER-LY SANDOZ, or BASEL, SWITZERLAND PROCESS or MAKING nIALxYL BARBITURIo ACIDS AND ppma 2,3. 'nI nTHY -L DIMETHYLAMINO --IPYR AZOLON .equimolecular quantities of the components or by dissolving them in solvents and evaporatin the same. The products thus obtaine especially when prepared by melting, less of a yellowish color, which color is probably due to a partial oxidation of the pyrazolone derivative.

It has now been found that the compounds of 5,5-disubstituted barbituric acids and 1- phenyl 2,3 dimethyl l-dialkylamino-5-pyrazolones can be obtained in a very pure state and often in a colorless or only slightly yellowish crystalline form, if salts of 5,5-disubstituted barbituric acids and salts of 1- phenyl -2,3-dimethyl-t-dialkylamino-5-pyrazolones are allowed to interact in a saturated aqueous solution ofv the 1-phenyl-2,3-d1- methyl-L-dialkylamino-5-pyrazolene itself in the reaction.

If, for instance, the reaction is carried out in pure water and l-phenyl-2,3-dimethyl-4 dimethylamino-5-pyrazolone is employed, a product is obtained, which does not contain the molecular component, owing to the fact that the compound is partially hydrolyzed and the more easily soluble pyrazolone derivative partly dissolved in water. This dissolution does not, take place if a saturated aqueous solution of the pyrazolonederivative is used as a solvent.

The products thus obtained are purer even without a subsequent recrystallization, than those prepared according to the processes oWn at present. They are colorless crystalline compounds, which are diflicultly soluble in water, soluble in alcohol and methanol and possess analgetic and soporific properties.

For carrying out this process it is not absolutely necessary to start from the isolated salts of 5,5-disubstituted barbituric acid the reaction mayalso be performed with a solution which has been prepared by adding the calculated quantity of an alkali, for instan B is slowlyiad'ded,

quantity of the pyrazolone caustic soda, to a suspension of a barbituric acid inv a saturated aqueous solution .0f}1 phenyl -2,3 dimethyl 41- dialkylamino -'5'- pyrazolone.- V i The following examples illustrate'the'invention, theparts being by-w'eight': i

1; 224 parts of isobutylall'ylbarbituric acid are suspended in 1500-parts of a saturated aqueous solution of l'-phenyl'-2,3 dimethyl ldimethylamino-5-pyrazolone and brought 7' into solution: by addition of- O parts o'f'sodium hydroxide; The solution thusobtained under stirring, to a solution of 231 parts of 1-phenyl-2,3Qdimethyl l-di methylaminqS-pyrazolone in 1000 partsof normalhydrochloric acid,which solution is subsequently saturated with 1-p'hen'yl-2,3'-,di-

methyl-4 dimethylamind5-pyrazolone.

The salt-like dles; "Its fusion pointis 878 9 C. under previous sintering. r The otherpropertie's are the same as des'cribed inthe U; S; specification N 0. 1,655,795. I

2; 206 parts of the sodium salt of diethylbarbituric acid: are dissolved in 2000 parts of a saturated aqueous solution of 1-phenyl-2,3 dimethyldimet'hylamino-5-pyrazolone and added as indicated in Example 1 toa solution Of--231 parts of l1'-phenyl-2,3 -dimethyl 4 dim'ethyl'amino-5-pyrazolone' in 1000 parts of normal hydrochloric acid (this solution is previously saturated with the same pyra' razolone prev-iouslys'a turated with th'is'com- No Drawing. Application filed November 20, 1928, SerialNo. 320,763, and in Switzerland December 3," 1 9 27.

The compounds of 5,5-disubstituted bar bituric acids and 1-phenyl-2,3-dimethyl-4- compoundimmediately'sepa rates out in slightly yellowish drops which soon solidifyto'nearly colorless" crystal nee pound; The reaction product separates out,

0 Q h Qh s lidifies to crysta need es F;P'- 97-"0.-

4. 254 parts of the sodium salt of phenylethylbarbituric acid are brought into interaction with a solution of 231 parts of '1- phenyl-2,3- dimethyl-4-dimethylamino-5 -pyrazolone, prepared according to the preceding examples. The oily separating products soon solidify to nearly colorless crystals of F. P. 132-134: C.

' 5. 246 parts ofthe sodiumsalt of n 'butyl allybarbituric acid are dissolved in 2000 arts of a saturated aqueous solution of 1- phenyl-2,3- -dimethyl-4-dimethylamino 5-pyrazolone and allowed to interact with 231 parts of 1-phenyl-2,3 dimethyl 4-dimethylamino-5-py'razolone dissolved'in 1000 parts amino-B-pyrazolone obtained by the interaction of an alkali metal saltof the former and a strong mineral acid salt of the latter in form of a saturated aqueous solution, said compound constituting a colorless crystalline product, difiicultly sol ble in water, soluble in alcohol and methanol, possessing analgetic and s'oporific properties and having its melting point at.70.-719 O.m 1

In witness whereof I have hereunto signed my name this 8th day of November, 1928. i

' I FRITZ MULLER.

ofno'rmal sulphuric acid .(the solution is beforeits use saturated with'the same, pyrazolone derivative); The compound soon separates out in form of colorless, fine crystals. F. P. 91? C.

6. 2% parts of isobutylallylbarbituric acid poundsoon separates out in nearly colorless I drops, which solidify to white very fine crystal needles. The compoud meltsafter dryingat '707 1 C i -7. 224: parts,of isobutylbarbituric acidand V 259 parts of l-phenyl-QB-dimethyllediethylamino-5 -pyrazolone are allowed to interact in the manner as indicated in thepreceding examples. The new compound first separates out in a pasty mass which solidifies to a White microcrystalline powder. F. P.-72 0..

What, I claim is:

' 11-. A process for the preparationof com- 0 pounds of 5,5;disubstituted barbituric acids and l -phenyl-2,3 dimethyl-4-dialkylamino 5-pyrazolones, consisting-1n the interaction of alkali metal salts of 5,'5-disubstituted barbituric acids and strong mineral .acid salts of -1 l-phenyl 2,3- dimethyL-dialkylamind5 pyrazolones, the latterbeing used in form of a saturated aqueous solution forming solvent for thedoubledecomposition. I

2. Aprocess for the preparationpf compounds of 5,5.-'disubstituted barbituric acids and 1-phenyl-2,3-dinaethyl-4-dimethylamino- 5 -pyrazolone, consisting in the-interaction of alkali metal salts of 5,5-disubstituted barbi- 'turic acids and strongmineral acids salts of l phenyl-2i,3 dimethyl- 4- dimethylamino- 5- pyrazolone, the latter being used in form of 9.

- saturated aqueous solution forming solvent.

3. As; anew articleof manufacture.the new. compound of isobutylallylbarbituric acid and 1-phenyl-2,3-dimethyl 4'-dimethy1- 

